COVID-19 Response Support

Coronavirus (COVID-19) Update: FDA Continues to Accelerate Development of Novel Therapies for COVID-19 

• As part of the Trump Administration’s all-hands-on-deck approach across public, academic and private sectors to combat the COVID-19 pandemic, the U.S. Food and Drug Administration stood up a new program to expedite the development of potentially safe and effective life-saving treatments. The program, known as the Coronavirus Treatment Acceleration Program (CTAP), is using every tool at the agency’s disposal to bring new therapies to sick patients as quickly as possible, while at the same time supporting research to further evaluate whether these medical countermeasures are safe and effective for treating patients infected with this novel virus.
  
  There are a large number of companies and researchers developing and evaluating COVID-19 related therapies. Given the urgent nature of the pandemic, under the FDA’s accelerator program, staff from the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research are providing regulatory advice, guidance and technical assistance as quickly as possible. As part of this work, the FDA is triaging requests from developers and scientists seeking to develop new drug and biologic therapies, getting the relevant FDA staff in touch with them and providing rapid, interactive input to get studies underway quickly. For example, the FDA has reviewed study protocols within 24 hours in many cases and has reviewed single-patient expanded access requests generally within three hours. The FDA is also collaborating with federal partners, developers and researchers to create protocols that can be used across institutions and programs to streamline efforts.
  
  Requests for product development for proposed COVID-19 uses and drug development should be sent to covid19-productdevelopment@fda.hhs.gov. 

FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic

FDA has pulled together some general information that may be useful to sponsors wishing to rapidly initiate interactions with the FDA regarding potential development of therapeutics for the COVID-19 virus.

If you feel your investigational product may have activity against the COVID-19 virus and have relevant cell culture and/or animal model data, you may submit a Pre-IND (PIND) application to the Agency as a “general correspondence.” FDA highly recommends that you include all relevant information for review. If you feel your product’s stage of development warrants a formal Pre-IND meeting, please refer to the Division of Antivirals Pre-IND letter of Instruction website for details.

• A pre-assigned PIND number can be obtained from the following website: Requesting a Pre-Assigned Application Number
• Sponsors can submit their PIND submissions(s) either electronically or via paper.
• Electronic Submission Information (via ESG)
• For information about submitting electronically to CDER, please see the website: Electronic Common Technical Document (eCTD)
• For any questions regarding electronic submissions in general, please email CDER’s Electronic Submissions Support Team at ESUB@fda.hhs.gov or call Valerie Gooding at 301-796-0902.
• Paper Submission Information
• Please submit 3 paper copies and a CD containing the submission to the following address:

• Food and Drug Administration
  Center for Drug Evaluation and Research
  Division of Antivirals
  5901-B Ammendale Road
  Beltsville, MD 20705-1266

Note, if you don’t have activity information, but believe your product may have potential against the COVID-19 virus, you may find it useful to consult the National Institutes of Health, Division of Microbiology and Infectious diseases website which contains information about preliminary screening activities that may be available to potential sponsors of antiviral products. If you do not have specific information related to the COVID-19 virus, but still feel that your product warrants a PIND, then please include as much information as you can and a rationale for review.

Please also note the U.S. government has launched a website for stakeholders who wish to submit market research packages related to potential uses of products during the current outbreak: 2019 Novel Coronavirus (Medical Contermeasures.gov).

Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.

Any drug being developed to treat or prevent a condition with no current therapy obviously is directed at an unmet need. If there are available therapies, a fast track drug must show some advantage over available therapy, such as:

• Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
• Avoiding serious side effects of an available therapy
• Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
• Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
• Ability to address emerging or anticipated public health need

• More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval

• More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers

• Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met

• Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

Fast Track designation must be requested by the drug company. The request can be initiated at any time during the drug development process. FDA will review the request and make a decision within sixty days based on whether the drug fills an unmet medical need in a serious condition.

Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.

EMA’s Human Medicines Committee (CHMP) has published a statement urging the EU research community to prioritise large randomised controlled studies because they are most likely to generate the conclusive evidence needed to enable rapid development and approval of potential treatments of COVID-19. The statement promotes a harmonized approach to data collection and a robust methodology for COVID-19 clinical trials across the EU to make best use of the available supply of investigational agents. It emphasizes the need to include all EU countries in these trials.

• EMA says it is working with stakeholders to support the conduct of clinical trials for COVID-19 in Europe and that it will “support medicine developers with all available regulatory tools to advance and expedite the development of effective measures to fight and prevent the spread of COVID-19.”
• EMA said it would waive fees for its scientific advice to developers of treatments and vaccines for the virus.
• Companies wishing to submit a CTA to the agency are instructed to submit it both via the normal Common European Submission Portal (CESP) and directly to MHRA via its clinical trial helpline.

expedited Ethics Committee opinion

Points to consider on implications of Coronavirus diseaseGuidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic

Global regulators map out data requirements for phase 1 COVID-19 vaccine trials

Implications of coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials

The MHRA is ready to prioritise and provide any assistance for clinical trials applications submitted for COVID-19

Prioritising COVID-19 assessments - MHRA have procedures for rapid scientific advice, reviews and approvals and are ready to support manufactures, researchers and other regulators. MHRA have dedicated resources to ensure this happens, as they did during the Ebola crisis when they authorised clinical trial applications within a week.

Submitting COVID-19 applications - Please submit any applications directly to the Clinical Trial Helpline by emailing clintrialhelpline@mhra.gov.uk, as well as through the normal CESP route so MHRA can begin work as soon as possible. MHRA will then liaise closely with any applicants to ensure it’s managed as efficiently as possible.

• If you want advice of any aspect of a clinical trial, call or email MHRA’s Clinical Trials Unit on clintrialhelpline@mhra.gov.uk or 020 3080 6456.
• You can also contact the HRA who can advise on expedited Ethics Committee opinion.

Naming your study - As requested by the WHO, please ensure that the WHO official acronym for the coronavirus disease (COVID-19) is entered in the title field of the trial registration data set (Annex 1 XML). This will facilitate finding and extracting clinical trials related to COVID-19 from public databases.

More Links:

Advice for Management of Clinical trials in relation to Coronavirus

MHRA Good Practice (GxP) inspections during the COVID19 outbreak

MHRA Guidance on Coronavirus

MHRA guidance on coronavirus (COVID-19)

WHO on 20 March announced the launch of SOLIDARITY, an unprecedented, coordinated push to collect robust scientific data rapidly during a pandemic. The study, which could include many thousands of patients in dozens of countries, has emphasized simplicity so that even hospitals overwhelmed by an onslaught of COVID-19 patients can participate. WHO's website will randomize patients to local standard care or one of the four drug regimens, using only ones available at the patient's hospital. Physicians will simply record the day the patient left the hospital or died, the duration of the hospital stay, and whether the patient required oxygen or ventilation. “That's all,” says Ana Maria Henao Restrepo, a medical officer at WHO's Department of Immunization Vaccines and Biologicals.

• $8 million to identify and develop antiviral therapies for people infected with COVID-19.   
• $5 million for clinical trials to better treat and manage COVID-19 patients with severe acute respiratory distress, which can be fatal. 

This funding is in addition to the $2 million already allocated from the MRFF for research into a vaccine against COVID-19. 

More Links:

COVID-19: Guidance on clinical trials for institutions, HRECs, researchers and sponsors

Minister of Health approved an Interim Order Respecting the Importation and Sale of Medical Devices for Use in Relation to COVID-19. The interim order will enable an expedited review of medical devices indicated to diagnose, treat, mitigate or prevent COVID-19, at no cost

In an effort to facilitate earlier access to a vaccine, or therapeutic product for COVID-19, the Department will expedite the review of any COVID-19 related health product submissions and applications. Doing this will ensure timely access to novel therapies without compromising the safety, efficacy and quality of products.

Sponsors wishing to file a submission or application should contact the appropriate review bureau.

More Links:

Management of clinical trials during the COVID-19 pandemic: Notice to clinical trial sponsors

Extraordinary measures for clinical trials due to COVID-19

The Irish HPRA has postponed all routine compliance inspections at the regulated sites until further notice and has informed all sites that would have received an inspection notice. The conduct of triggered and EMA requested inspections will be decided on a case-by-case basis and may be conducted remotely. Should we believe an urgent on-site inspection is necessary, the HPRA will follow public health advice in relation to any required precautions.

HPRA will give priority review to any submission relating to COVID-19. In order to assist HPRA in the identification of such submissions, the cover letter associated with the submission should be clearly marked “COVID-19 relevant”; a justification as to why the submission is COVID-19 relevant should also be included in the cover letter. Furthermore, the email sent to submissions@hpra.ie should also be clearly marked “COVID-19 relevant” in the subject line. These actions by our stakeholders will ensure appropriate prioritisation of assessment, which may be expedited in line with national and/or EU legal frameworks.

Italian Medicines Agency

Clinical trials’ management in Italy during the COVID-19 (coronavirus disease 19) emergency

Ministry of Health, Labour and Welfare of Japan (MHLW) issued a notice announcing a waiver of the statutorily-required waiting period after submitting a request for clinical trial to the MHLW in respect of treatments related to COVID-19. Typically, any person or legal entity that submits a request for clinical trial to the MHLW must wait 30 days from the date of request before starting a clinical trial, in order for the MHLW to investigate health and sanitary issues that may occur in connection with the proposed trial (Article 80-2, Paragraph 3 of the Pharmaceuticals and Medical Devices Act). However, the new circular notice enables pharmaceutical companies, medical device companies, and doctors to start clinical trials for drugs or medical devices that are considered necessary to prevent and/or treat COVID-19 without the 30-day waiting period.

Netherlands Central Committee on Research Involving Human Subjects

Recommendations for the conduct of clinical research at the time of restrictive measures due to the coronavirus